Abstract
Photodynamic therapy (PDT) necessitates approaches capable of increasing antitumor effects while decreasing nonspecific photodamage. We herein report an activatable probe (Glu-PyEB) comprising two distinct photosensitizers with mutually suppressed photodynamics. Activation by tumor-associated γ-glutamyltranspeptidase gives rise to a generator of superoxide radical (O2-•) accumulated in lysosomes and a producer of singlet oxygen (1O2) enriched in mitochondria. This enables light-irradiation-triggered damage of lysosomes and mitochondria, robust cell death, and tumor retardation in vivo, showing the use of paired photosensitizers subjected to reciprocally suppressed photodynamics for activatable PDT.
Keywords:
activatable; dual photosensitizers; dual-organelle; photodynamic therapy; γ-glutamyltranspeptidase.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Biocompatible Materials / chemical synthesis
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Biocompatible Materials / chemistry
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Biocompatible Materials / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Drug Screening Assays, Antitumor
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Female
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Humans
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Materials Testing
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Molecular Structure
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Organelles / drug effects*
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Particle Size
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Photochemotherapy*
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Photosensitizing Agents / chemical synthesis
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Photosensitizing Agents / chemistry
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Photosensitizing Agents / pharmacology*
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Reactive Oxygen Species / metabolism*
Substances
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Antineoplastic Agents
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Biocompatible Materials
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Photosensitizing Agents
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Reactive Oxygen Species